靶向巨噬细胞的癌症治疗策略
Macrophage-directed therapeutic strategies in cancer.
肿瘤相关巨噬细胞(TAMs)是肿瘤微环境的主要组成部分,具有显著的功能可塑性,根据所处的微环境信号,既可表现为促进肿瘤进展的免疫抑制细胞,也可表现为支持抗肿瘤免疫的免疫刺激细胞。
英文原题:Novel immunotherapies for prostate cancer.
自2010年基于自体树突状细胞的疫苗sipuleucel-T问世以来,晚期前列腺癌免疫治疗方法的临床开发在很大程度上一直处于停滞状态。
自2010年自体树突状细胞疫苗sipuleucel-T问世以来,晚期前列腺癌免疫治疗方法的临床开发在很大程度上一直处于停滞状态。除了在罕见的分子筛选患者中偶尔使用pembrolizumab免疫检查点阻断外,尚无其他免疫方法获得监管批准。成功临床开发面临诸多挑战,包括免疫排斥型肿瘤免疫微环境、缩小治疗窗口的脱靶和/或炎症毒性,以及抗肿瘤反应持久性有限。然而,近期药物设计和细胞工程方面的进展重新激发了人们对前列腺癌新型免疫治疗方法兴趣。本综述概述了前列腺癌新型免疫治疗临床开发的当前格局,重点关注已产生有前景早期临床数据的嵌合抗原受体(CAR)T细胞、T细胞衔接器、单克隆抗体和癌症疫苗方法。
Since the advent of the autologous dendritic cell-based vaccine, sipuleucel-T, in 2010, the clinical development of immunotherapeutic approaches in advanced prostate cancer has largely been lacking. Aside from the infrequent use of pembrolizumab immune checkpoint blockade in rare molecularly-selected patients, no further immune approaches have achieved regulatory approval. Numerous challenges exist that preclude successful clinical development, including an immunologically-excluded tumor immune microenvironment, off-target and/or inflammatory toxicities that narrow the therapeutic window, and limited durability of anti-tumor responses. Nevertheless, recent advances in drug design and cellular engineering have reinvigorated interest in novel immunotherapeutic approaches in prostate cancer. This review provides an overview of the current landscape of novel immunotherapy clinical development for prostate cancer, with a focus on chimeric antigen receptor (CAR) T cells, T cell engagers, monoclonal antibodies, and cancer vaccine approaches that have produced promising early phase clinical data.
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